Hayashibara Assessment of “Nature” Article, and Statement on Safety of TREHA(R) (trehalose)

OKAYAMA, Japan, Feb. 13, 2018 /Kyodo JBN/ —

Hayashibara Co., Ltd.

Hayashibara Assessment of “Nature” Article, and Statement on Safety of TREHA(R) (trehalose)

In regards to the recently published article "Dietary trehalose enhances virulence of epidemic Clostridium difficile" in the journal Nature, Hayashibara Co., Ltd. would like to share its assessment of web-based comments, news and blogs, and make a statement on the safety of its product, TREHA(R) (trehalose), as a manufacturer of trehalose.

1. Relationship between the regulatory status of trehalose in and outside Japan, and the epidemic outbreaks of Clostridium difficile (CD)TREHA(R) (trehalose) was launched in 1995 in the Japanese market and then introduced outside Japan. Since then, TREHA(R) (trehalose) has been used in Japan in a wide variety of foods by many customers for over 20 years. The Nature article discusses that the virulent epidemics are concurrent with the regulatory status of trehalose “approvals” in the United States (GRAS in 2000) and Europe (Novel Food in 2001); however, no epidemics of any kind were noted in Japan in the 5 years previous to the “approvals” of trehalose in the United States and Europe.

According to the diagram in the article, there was a virulent CD epidemic outbreak in Canada around 2003. However, TREHA(R) (trehalose) was not available in the market or used in any food items in Canada until its approval in mid-June 2005. In addition, the regulatory status of trehalose did not allow for its import or use in several of the other countries described in the article such as Kuwait, Costa Rica, Iran and Panama, where epidemic outbreaks were confirmed.

Based on Hayashibara’s estimate of the intake of trehalose from natural foods and ingredients in a normal diet in the United States, the intake of Hayashibara’s trehalose would be minimal, less than 5% of the naturally occurring trehalose in general food items. This is unlikely to justify the concurrence of the epidemic outbreaks.

Considering these facts, Hayashibara believes the presence of TREHA(R) (trehalose) in the food industries of the described counties does not support the conclusion of the correlation that is cited in the article.

2. Test results on animalsThe study employed a specific test system that challenged mice with the virulent strains after treating them with 6 types of antibiotics to sterilize their intestinal bacteria. Because the C57BL/6 mice have trehalase, an enzyme that breaks down trehalose in their small intestines, it is highly likely that the trehalose given to the mice broke down into glucose and was subsequently absorbed as glucose in the small intestine. This process is identical to that of oral administration of glucose or other disaccharides. Another dispute is that the study does not show comparative results with other carbohydrates containing glucose as a carbon source.

3. Effects of trehalose on intestinal bacteriaIn humans and other mammals, trehalose is hydrolyzed to glucose by trehalase, which is located in the small intestine. The glucose is subsequently absorbed in the small intestine as glucose, as explained above. It is Hayashibara’s contention that the amount of trehalose in an intact form reaching the large intestine is too small to initiate any significant effects on intestinal bacteria.

A human oral clinical test conducted at the University of Colorado confirmed that consumption of 100g/day of trehalose for 12 weeks by subjects with an average age of 64 years resulted in no severe side effects, including bowel inflammation (Aging (2016) 8, 1167–1183).